H1 histamine receptor (H1HR) belongs to the family of rhodopsin-like G-protein-coupled receptors. Recent studies have shown that H1HR expression is increased in several types of cancer. However, its functional roles in tumor progression remain largely unknown, especially in hepatocellular carcinoma (HCC). We found that H1HR is frequently unregulated in HCC, which is significantly associated with both recurrence-free survival and overall survival in HCC patients. Functional experiments revealed that H1HR promoted both the growth and metastasis of HCC cells by inducing cell cycle progression, formation of lamellipodia, production of matrix metalloproteinase 2, and suppression of cell apoptosis. Activation of cyclic adenosine monophosphate-dependent protein kinase A was found to be involved in H1HR-mediated HCC cell growth and metastasis. In addition, we found that overexpression of H1HR was mainly due to the downregulation of miR-940 in HCC cells. Moreover, the H1HR inhibitor terfenadine significantly suppressed tumor growth and metastasis in an HCC xenograft nude mice model. Our findings demonstrate that H1HR plays a critical role in the growth and metastasis of HCC cells, which provides experimental evidence supporting H1HR as a potential drug target for the treatment of HCC.

中文翻译：

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组胺受体 H1 的上调促进肿瘤进展并导致肝细胞癌的不良预后。

H1 组胺受体 (H1HR) 属于视紫质样 G 蛋白偶联受体家族。最近的研究表明 H1HR 表达在几种类型的癌症中增加。然而，其在肿瘤进展中的功能作用仍然未知，尤其是在肝细胞癌 (HCC) 中。我们发现 H1HR 在 HCC 中经常不受调节，这与 HCC 患者的无复发生存率和总生存率显着相关。功能实验表明，H1HR 通过诱导细胞周期进程、片状伪足的形成、基质金属蛋白酶 2 的产生和抑制细胞凋亡来促进 HCC 细胞的生长和转移。发现环磷酸腺苷依赖性蛋白激酶 A 的激活参与 H1HR 介导的 HCC 细胞生长和转移。此外，我们发现 H1HR 的过表达主要是由于 HCC 细胞中 miR-940 的下调。此外，H1HR 抑制剂特非那定显着抑制了 HCC 异种移植裸鼠模型中的肿瘤生长和转移。我们的研究结果表明 H1HR 在 HCC 细胞的生长和转移中起着关键作用，这为支持 H1HR 作为治疗 HCC 的潜在药物靶标提供了实验证据。